Direct estimation of the frequency of human cytotoxic T lymphocytes and their precursors following in vitro allosensitization

Cell mediated lympholysis (CML) has been proposed as an in vitro model of the rejection process that results from transplantation of allogeneic tissue. To date, the absolute frequencies of cytotoxic T lymphocytes (CTL) and their precursors (CTL.P) have not been directly estimated in man because of technical difficulties. Through optimizing the conditions for radiometric detection of 51Cr release and the attendant improvement in CML sensitivity, direct CTL frequency estimates have been determined in peripheral blood (PBL), spleen (SPL), and lymph nodes (LNC) after in vitro allostimulation using unrelated human cells and limiting dilution assays. The mean frequency of CTL generated from PBL is 1 in 826 cells (0.121% +/- 0.101%) which, from preliminary experiments, is significantly greater than that generated from either LNC or SPL (p less than 0.05). With restimulation of primed cells on day 10, the frequency of CTL generated from PBL was increased 400%. The CTL.P frequency (0.0064% +/- 0.0050%) was approximately 5% of the corresponding CTL frequency. The CTL.P frequencies were found to be minimal estimates as both accessory "filler" cells and T cell growth factors increased the level of detection of CTL.P an average of threefold. The limiting cell dilution assay as detailed in this report should be a powerful tool for defining the cellular requirements and related factors necessary for optimal induction of a CTL response and should provide the means for determination of the immunogenetic requirements and the allospecificity of human cytotoxic lymphocytes.     

Association between HLA and Japanese patients with rheumatoid arthritis

Japanese patients with rheumatoid arthritis (RA) were observed to have a statistical association with HLA-DR4, MT3. Strong association between the clinical severity of RA and HLA was also observed. Male patients had a stronger association with HLA than female patients. Males are more resistant to RA than females. This suggested that the threshold of liability for RA is higher in males than in females. Japanese patients with RA with systemic vasculitis were negative for HLA-Bw44 and had antilymphocytotoxic autoantibody, indicating that RA with systemic vasculitis is different in etiology from RA without systemic vasculitis.     

Saccades and multisaccadic gaze shifts are gated by different pontine omnipause neurons in head-fixed cats

 Pontine omnipause neurons (OPNs) have so far been considered as forming a homogeneous group of neurons whose tonic firing stops during the duration of saccades, when the head is immobilized. In cats, they pause for the total duration of gaze shifts, when the head is free to move. In the present study, carried out on alert cats with fixed heads, we present observations made during self-initiated saccades and during tracking of a moving target which show that the OPN population is not homogeneous. Of the 76 OPNs we identified, 39 were found to have characteristics similar to those of previously described neurons, ”saccade” (S-) OPNs: (1) the durations of their pauses were significantly correlated with the durations of saccades; (2) the discharge ceased shortly before saccade onset and resumed before saccade end; (3) visual responses to target motion were excitatory; and (4) during tracking, S-OPNs interrupted the discharge for the duration of saccades and resumed firing during perisaccadic ”drifts”. However, the characteristics of 37 neurons (”complex” (C-) OPNs) were different: (1) the pause duration was not correlated with the duration of self-initiated saccades; (2) time lead of pause onsets relative to saccades was, on average, longer than in the group of S-OPNs, and firing resumed after the saccade end; (3) visual target motion suppressed tonic discharges; and (4) during tracking, firing was interrupted for the total duration of gaze shifts, including not only saccades but also perisaccadic ”drifts”. We conclude that cat OPNs can be subdivided into two main groups. The first comprises neurons whose firing patterns are compatible with gating individual saccades (”saccade” OPNs). The second group consists of ”complex” OPNs whose firing characteristics are appropriate to gate total gaze displacements rather than individual saccades. The function of these neurons may be to disinhibit pontobulbar circuits participating in the generation of saccade sequences and associated perisaccadic drifts. Received: 20 January 1998 / Accepted: 22 October 1998     

在单个细胞水平上研究自然杀伤细胞与肿瘤的相互作用

本文报告了自然杀伤细胞(NK)在单个细胞水平上与肿瘤细胞相互作用的特征及机制,以及这一作用与自然抗体及自然进出(emperipolesis)瘤细胞的淋巴细胞(NEC)间的相互关系,提出了一个新的NK杀伤机制假说:“靶细胞自杀模式”。这对指导临床用免疫学方法治疗肿瘤可能有实际意义。本文还对淋巴细胞自然进出瘤细胞的特征及其与NK的关系和与肿瘤细胞相互作用的结局及意义作了详细的讨论.     

递进式目标康复护理对老年股骨颈骨折人工置换患者的临床效果

目的：探究递进式目标康复护理对老年股骨颈骨折人工置换患者术后功能恢复的影响及护理体会。方法：选取河南大学第一附属医院2018年6月至2020年8月期间收治的112例老年股骨颈骨折人工置换患者,按照手术先后顺序分为观察组和对照组,各56例。对照组患者实施常规护理,观察组患者实施递进式目标康复护理干预,比较两组患者自我效能水平、髋关节功能及日常活动能力。结果：干预后观察组患者自我效能、髋关节功能、日常活动能力评分均高于对照组,差异具有统计学意义（P <0.05）。结论：递进式目标康复护理干预的应用对促进老年股骨颈骨折人工置换患者自我效能水平,提高术后髋关节功能恢复情况,改善其日常活动能力等方面均具有较高的可行性。     

基于UHPLC-QTOF-MS/MS和分子对接筛选紫菀中润肠通便的效应

目的 通过UHPLC-QTOF-MS/MS和分子对接技术阐明紫菀Aster tataricus中润肠通便作用的效应成分。方法 采用UHPLC-QTOF-MS/MS技术分析体内肠道内容物的成分,再利用SYBYL-X 2.0与Discovery Studio 4.0分子对接软件研究肠道内容物成分与M2受体、M3受体、蛋白激酶C(protein kinase C,PKC)蛋白的相互作用,明确各成分与靶标蛋白的结合强度。结果 体内肠道内容物中共鉴定出28个紫菀中的化学成分,有10个成分均可与M2受体、M3受体及PKC蛋白分子对接较好,其中astin J与3种靶标蛋白结合的平均打分值最高,这些成分均以非共价键方式与靶标蛋白结合,产生氢键、范德华力、经典作用力等相互作用。结论 紫菀中的astin J、asterin F、asterin A、异绿原酸A、异绿原酸B、异绿原酸C、绿原酸、槲皮素、山柰酚和木犀草素共10个成分可能是通过调节M受体及其下游信号通路PKC蛋白的表达发挥润肠通便的作用。     

胰腺癌精准治疗现状、挑战和未来

胰腺癌恶性程度高,总体疗效欠佳,目前采用手术、放疗和化疗为主的传统治疗方法,疗效的改善已到了瓶颈。随着基因测序和多组学研究的开展,越来越多的信号通路和可作用靶点被发现,相应的靶向和免疫治疗药物也越来越多,胰腺癌的治疗模式正在逐渐向靶向治疗方向发展,进入精准医疗时代。